Method of treating vaginitis

ABSTRACT

Lactulose has been found to be effective in the treatment of vaginitis.

United States Patent [191 Wootton [4 1 Jan. 14,1975

[ METHOD OF TREATING VAGINITIS [75] Inventor: Leslie William Wootton, Kingsdown near Sevenoaks, England [73] Assignee: U.S. Philips Corporation, New

York, NY.

22 Filed: July 9,1973

[21 Appl. No.2 377,518

[30] Foreign Application Priority Data July 18, 1972 Great Britain 3351/72 [52] US. Cl. 424/180, 424/120 [51] Int. Cl A61k 27/00 Primary Examiner-Stanley J. Friedman Attorney, Agent, or Firm-Frank R. Trifari; Norman N. Spain [57] ABSTRACT Lactulose has been found to be effective in the treatment of vaginitis.

9 Claims, No Drawings METHOD OF TREATING VAGINITIS The invention relates to a new and novel method for the treatment of women suffering from vaginitis.

Vaginitis, inflammation of the vagina, is brought about by several organisms. The causative agents are of protozoan as well as of fungal nature, to wit species of the genus trichomonas and candida e.g. Candida albicans respectively.

Vaginitis caused by Candida is also called vaginal moniliasis or simply moniliasis.

Vaginitis often occurs in women who are on the contraceptive pill. The affection manifests itself in irritation and an inconvenient discharge from the vulva.

Means are available to treat the affection, they are, however, not satisfactory.

It is a principle object of this invention therefore to provide a new and highly effective treatment for women suffering from vaginitis.

This as well as other objects of the invention will be apparent from the description that follows.

Quite surprisingly, it has now been found that vaginitis can be cured by the intravaginal administration of lactulose during only a few days.

Although its mode of action is not yet understood, the effect of the drug is remarkable. Generally, already after 4-7 days of treatment with the drug a considerable improvement is obtained, whereas after 7-14 days the disease is completely cured.

The experience gathered up to now reveals that several months after termination of the treatment there is still no recurrence, even if the woman is kept on the contraceptive pill. This is in sharp contrast with the results obtained with the drugs usually prescribed for this indication: antibiotics such as Nystatin and Pimafucin". It is however believed that these drugs give a faster relieve than lactulose.

Therefore in a special embodiment of the method according to the invention, the treatment with lactulose is preceded by or combined with a treatment with an antibiotic as Nystatin or Pimafucin during about 4 days.

The amount of lactulose given in the treatment according to the invention may vary within wide limits. Usually 4 to 10 grams of lactulose are administered, once or twice a day. Excellent results have been obtained with as small a dose as 5 grams once or twice a day.

Lactulose may be administered as such or mixed with one or more carriers such as glucose, galactose or lactose.

A frequently used composition is a syrup containing about 50% by weight of lactulose, about 5% by weight of lactose, about 8% by weight of galactose and the remainder water. This composition is called hereinafter Duphalac.

When this composition or an other liquid, lowviscous composition is used, the patient should keep to a supine position for at least half an hour after the intravaginal instillation.

The problem of the retention of low-viscous liquid compositions can easily be avoided by soaking an ordinary intravaginal tampon, such as used during menstrual periods, with the amount of the composition to be administered.

Lactulose may also be administered in the form of a dry composition, for example one containing about 40% by weight of lactulose, about 4% by weight of lactose, about 6% by weight of galactose and the remainder dextrine maltose.

The use of formed compositions such as capsules, for example gelatine capsules or intravaginal tampons loaded with lactulose, whether or not to be wetted with water before instillation, is to be preferred because of the ease of their handling. Also pastes and formed compositions, such as suppositories and vaginal tablets may be used. The usual carriers may be employed to prepare these formed compositions.

Viscous liquid compositions can be easily prepared on the basis of Duphalac, using jellifying agents, such as pectine or gelatine, thickening agents such as tragacanth gum, arabic gum or carboxy methyl cellulose. If desired, colouring agents admitted for drugs and conserving agents such as sorbic acid and its salts may be added to compositions to be used in the method according to the invention.

As examples of such viscous liquid compositions may be mentioned:

a. 227.7 g of Duphalac, 45 g of polyethyleneglycol 4000 and 15 g of polyethyleneglycol 400 are heated at C until a homogeneous mixture is obtained. The mixture is cooled down and stirred with 12.5 ml of water to a viscous homogeneous liquid.

b. 284.7 g of Duphalac is heated to C. While stirring 3 g of tragacanth and 10 ml of water are added. After standing overnight water is added while stirring to obtain a homogeneous composition having a net weight of 300 g.

c. 284.7 g of Duphalac, 4.5 g of sodium carboxy methyl cellulose and 10 ml of water are mixed, heated, while stirring vigorously, to C and cooled down. After standing overnight water is added to a net weight of 300 g and the mixture is homogenized by stirring.

d. 284.7 g of Duphalac is heated to 70C. While stirring 45 g of gum Arabic is added. The mixture is cooled down and after standing overnight stirred to obtain a homogeneous mixture.

e. To 284.7 g of Duphalac while stirring 3 g of gelatine is added slowly. l2 mls of water are added and the mixture is heated to about 90C while stirring to obtain a homogeneous liquid. Water is added to a net weight of 300 g and the mixture is again homogenized.

The invention will now be described in greater detail with reference to the following case reports.

1. M. T., female, age 35, has been suffering from re-' current vaginal moniliasis with profuse discharge and vulval irritation for 2 years. She is on the contraceptive pill. Several courses of treatment with Nystatin pessaries, containing 10 international units, each for 10 days, have temporarily cured the symptoms, but reinfection has occurred each time within 3 to 4 weeks of stopping treatment.

She was seen on Aug. 15th, 1970 with a further recurrence, the symptoms being severe vulval irritation and copious discharge. She was treated with once daily vaginal instillation of Duphalac, 15 ml* by syringe, keeping to a supine position for at least half an hour after the dose. The course was continued for 2 weeks. The specific weight of Duphalac is 1.33.

4 Days after start of treatment, discharge and irritation had completely cleared. There has been no recurrence since 16 months later. The patient is still on the contraceptive pill.

2. S. L., female, age 28, suffering from recurrent vaginal moniliasis for years, complaining of heavy discharge and irritation following periods. Several periods of treatment with Nystatin have been only moderately successful. She was seen on Sept. 1st, 1971 and was treated with a 5 day course of Nystatin pessaries, followed by intravaginal application of Duphalac once daily. The treatment was applied using a tampon dipped in Duphalac syrup (up-take 7,5 ml) and inserted into the vagina just before retiring to stay there till the morning.

Within 3 days the infection cleared and she has had no further recurrence. There has been no further need for any treatment.

3. M. J., age 37, 1 years history of recurrent monilial vaginitis, treated with three separate courses of Nystatin pessaries. Despite some success each time, recurrence has taken place immediately after the succeeding menstrual period.

Nystatin was instituted a fourth time, for 5 days, a pessary being inserted twice daily, with some lessening of symptoms. Duphalac was given intravaginally by tampon soaked in Duphalac (up-take 6 to 7,5 ml) night and morning for 7 days following this.

Since the end of the course, the symptoms have stopped and have not recurred since, i.e. 3 months later.

4. S. M., age 21, a vaginal discharge since her marriage 18 months ago, causing irritation and embarrassment. After several different pessary treatments with poor results the discharge and irritation never disappearing completely laboratory tests showed a severe monilial infection. Nystatin pessaries were used, one twice daily for days, withsome lessening of the discharge and swelling, but not complete resolution.

Duphalacsoaked tampons containing 6 to 7.5 ml of Duphalac were then inserted twice daily for 7 days. Within 3 days the irritation and swelling had gone, and at the end of the course, the discharge was minimal and of no discomfort to the patient.

For 4 months the patient has been free of trouble.

5. A. J age 33, an unmarried woman on a mixed oestrogen/progestogen contraceptive for 3 years, she

has chronic recurrent vaginitis, having had Nystatin, Flagyl 1(2-hydroxyethyl)2-methyl-5- nitroimidazole) and Magmiller (methylmercaptomethyl5(5-nitrofurfurylidene )-oxazolidinone-3 Pimafucin vaginal tablets containing 25 mg of Pimafucin and 1 mg of benzalkoniumchloride were given, 1 nightly for 21 days. Overlapping the last 4 days of this treatment, Duphalac-soaked tampons (6-7,5 ml of Duphalac) were prescribed twice daily for 10 days.

Since the end of the Duphalac treatment, there has been no recurrence, and this 4 months period is over twice as long as any period in the last three years in which she has been free from infection.

She is still taking the contraceptive.

6. S. C., age 45, a menopausal woman, suffered a chronic vaginal itch, with reddening and swelling of the vulva, for 2 months. Thought at first to be a hormone deficiency, it was treated unsuccessfully with oestrogens by mouth and Locan pessaries.

A swab showed a trichomonal infection, and she was given Naxogin (nitrimidazine) tablets, one tablet twice a day for 6 days. This partially cleared the irritation, but not completely. A tampon containing 6 to 7,5 ml of Duphalac was given twice a day for 10 days with resultant complete resolution of the condition.

She has been free of the trouble for one year.

7) S. L., age 32 dated her vaginal infection from the period around the birth of her last baby, now 2 years old. The baby had developed oral thrush at 1 month, but S. L. had no symptoms at that time. Being a nurse, she had linked in retrospect the thrush with her now copious discharge.

Tampons soaked with 6 to 7,5 ml of Duphalac were given twice daily, and she continued with treatment for 15 days. Improvement began on the 6th day and by the 13th she was free from discharge. Swabs taken before treatment showed a moderate growth of Candida albicans. Further post-Duphalac swab showed no candida.

There has been no recurrence for 6 months.

No other treatment had been used.

8. H. H., age 42 has complained from her early teens of vaginal discharge, which has been considered by previous doctors as neurotic, non-specific, cervicitis, but has never been cleared satisfactorily. On routine examination for smear testing, a copious white discharge was found, and it was suggested to her that she might try a newer treatment. Swab culture showed copious monilial growth.

Duphalac-soaked tampons (6-7,5 ml) were given twice daily, with considerable improvement being evident after only 7 days. By the twelfth day, the discharge had almost disappeared. She discontinued treatment on the 14th day, and was free from discharge for 3 weeks, an unheard-of occurrence.

2 days after she noted the return of the discharge she re-started Duphalac treatment, with the result that within 4 days she was better.

She has had no further recurrence in 2 months, despite having had two menstrual periods, which had always in the past exacerbated the symptoms.

9. T. 8., age 69, a small, undernourished, prematurely aged woman, she lives in a nursing home. Her senile vaginitis was an embarrassment to her and her fellow patients, and it was decided to attempt to improve her by giving Premarin tablets 1.25 mg daily. Although this improved her vaginal atrophy, she developed a monilial infection which was endemic in the nursing home.

Duphalac-soaked tampons (67,5 ml pro tampon) were used night and morning for 7 days with considerable relief to the patient within 4 days. One month later there was no recurrence of symptoms and the Premarin was being continued indefinitely.

10. F. M., age 23, had a vaginal discharge. A trichomonal infection was found. Duphalac-soaked tampons (6-7,5 ml) were given, one tampon being inserted night and morning. Within 4 days she was much better, and within 4 more days she had neither discharge nor irritation.

She has not returned for follow-up in 2 months.

I claim:

1. A method of treating women suffering from vaginitis which method comprises intravaginally administering to said women a daily effective amount of lactulose. 2. The method of claim 1 wherein lactulose is administered in an amount of 4 to 10 grammes once or twice a day.

3. The method of claim 2 wherein lactulose is administered daily in l or 2 doses of 5 grammes.

with an effective amount of lactulose.

7. The method of claim 4 wherein the lactulose syrup is contained in an intravaginal tampon.

8. Intravaginal tampon loaded with an effective amount of lactulose.

9. Intravaginal tampon of claim 8 loaded with an effective amount of a syrup containing about 50% by weight of lactulose, about 5% by weight of lactose, about 8% by weight of galactose and the remainder water.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 3,860,707

DATED 1 January 14, 1975 |NVENTOR(S) 1 LESLIE WILLIAM WOOTTON It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In the title page, Item [30 "3351/72" shouid be Signed and sealed this day of 1976.

Signed and Scaled this Thirtieth Day of November 1976 [SEAL] AIIeSI.

RUTH C. MASON C. MARSHALL DANN Arresting Officer Commissioner oflalenrs and Trademarks #1 43 UNITED STATES PATENT OFFICE CERTIFICATE OF CQRECTHON Patent No. 318601707 Januarv l4. 1975 I nwfls) LESLIE WILLIAM WOOTTON It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In the title page, under [75] Inventor:"

change "Leslie William Wootton,Kingsdown" to Leslie William Wootton, West Kingsdown change Yneat Sevenoaks,England" to near Sevenoaks, Kent England Signed and Scaled this twenty-ninth Day of July 1975 [SEAL] Arrest:

' RUTH c. MASON c. MARSHALL DANN Arresting Officer ('nmmisxinm'r ()[PUHIIIS and Trademarks 

2. The method of claim 1 wherein lactulose is administered in an amount of 4 to 10 grammes once or twice a day.
 3. The method of claim 2 wherein lactulose is administered daily in 1 or 2 doses of 5 grammes.
 4. The method of claim 1 wherein lactulose is administered in the form of a syrup containing about 50% by weight of lactulose, about 5% by weight of lactose, about 8% by weight of galactose and the remainder water.
 5. The method of claim 1 wherein the administration of lactulose is preceded by or combined with the intravaginal administration of a daily effective amount of an antibiotic selected from the group consisting of Nystatin and Pimafucin.
 6. The method of claim 1 wherein lactulose is administered in the form of an intravaginal tampon loaded with an effective amount of lactulose.
 7. The method of claim 4 wherein the lactulose syrup is contained in an intravaginal tampon.
 8. Intravaginal tampon loaded with an effective amount of lactulose.
 9. Intravaginal tampon of claim 8 loaded with an effective amount of a syrup containing about 50% by weight of lactulose, about 5% by weight of lactose, about 8% by weight of galactose and the remainder water. 